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L0301P61 - Immune System Overview
__TOC__ The Immune System *has two main components **innate immunity **adaptive immunity Innate Immunity *provide the initial defence against infections *fast acting but no memory *includes: **epithelial barriers **phagocytes and granulocytes **natural killer cells (lymphocytes) **the complement system **and dendritic cells which provide the link between innate and adaptive immunity Adaptive Immunity *responses develop later *are mediated by lymphocytes and their products *B lymphocytes —> antibodies **highly specific surface receptors ***can bind to invading pathogens ***are membrane bound but can be secreted as antibodies *T lymphocytes **specific receptors ***do not bind to the pathogen, but rather to a peptide derived from the pathogen presented in the MHC complex ***cannot produce antibodies Immune Cell Development *all blood cells form from the pluripotent haemopoietic stem cells in the bone marrow Common Lymphoid Progenitor *B cells *T cells *NK cells *dendritic cells Common Myeloid Progenitor *dendritic cells *granulocytes **neutrophil, eosinophil, basophil *macrophage progenitors **mast cells, monocytes —> macrophages *megakaryocytes **platelets *erythrocyte progenitors **erythrocytes (red blood cell) Maturation of Lymphocytes *development begins in the bone marrow *B cells remain in the bone marrow to mature *T (thymus-derived) cells mature in the thymus **undergo positive and negative selection **majority (97%) die during selection *migration to the periphery after maturation and is activated in lymph nodes or spleen Distribution of Lymphoid Tissues *lymph nodes found all around the body **drainage system of tissues, thus detects antigens in tissues *spleen **detects antigens that are blood borne Lymph Node Structure *antigen enters via afferent lymphatic vessels *T cells and B cells **enter through the artery via the high endothelial venules **after activation, leave the cell via the efferent lymphatic vessel Overview of Cellular Responses Associated with Innate Immunity #initial exposure #local cell response - signals for support #influx of phagocytic cells #clearing of pathogen by phagocytes #signal sent to exacerbate inflammation Inflammatory Response #bacteria trigger macrophages to release cytokines and chemokines #vasodilation and increase vascular permeability causes redness, heat and swelling #inflammatory cells migrate into tissue, releasing inflammatory mediators that cause pain The Complement System *complement proteins are constitutively present in serum *is a cascade of molecules binding and cleaving into smaller sub-fragments *triggered by **'classical pathway' ***binding to pathogen surfaces directly or immunoglobulins/antibodies on surface ***requires the adaptive immune system **via mannose-binding lectin (MBL) **'alternative (amplification) pathway' ***spontaneous hydrolysis of C3 *results in recruitment of immune cells, increased phagocytosis and formation of pores in pathogen surfaces   Mechanism #C3 cleaved into C3a and C3b #C5 cleaved into C5a and C5b #C3a and C5a involved in inflammation #C3b bind to pathogen to attract phagocytes - bacteria cannot be phagocytosed until C5a activates the macrophages #C5b attracts C6, C7,C8 and C9 to form a membrane-attack complex (MAC) which “punches” holes in the pathogen membrane Myeloid Cells Macrophage *phagocytosis and activation of bactericidal mechanisms *antigen presentation Dendritic Cell *antigen uptake in peripheral sites *antigen presentation Neutrophil *phagocytosis and activation of bactericidal mechanisms *most abundant white blood cell Eosinophil *killing of antibody-coated parasites Basophil *promotion of allergic response and augmentation of anti-parasitic immunity Mast Cell *release of granules containing histamine and active agents Neutrophils *a.k.a polymorphonuclear leukocyte *characterised by their lobulated nuclei *most abundant leukocyte in the blood **4000-10,000 per µl *not normally found in tissues *first to migrate to tissues in response to signal of microbial invasion *production of neutrophils increases in response to infection **up to 20,000/µl —> increased neutrophil count = immune response to infection *action is rapid and they die after few hours *pus found in infections = dead neutrophils Monocytes/Macrophages *less abundant than neutrophils 500-1000/µl *monocytes - blood, macrophages - tissue *first encounter with macrophage sets off a cascade of events (to eliminate microbe) **signal to immune system about breach **produce cytokines ***tumour necrosis factor (TNF) and IL-1 **inflammation: signal local endothelial cells ***to increase expression of adhesion molecules to allow better binding of neutrophils and monocytes at site ***to increase gap between cells to allow easier passage of cells and fluid into site of infection Eosinophils and Basophils *much less abundant than other cells in the blood *contain granules that are useful in function of the cell *associated with dealing with parasites and worms - too big to be phagocytosed **they are not large but “attack” in large numbers by releasing granules *basophils are associated with allergic reactions where their activation can cause tissue damage   Natural Killer (NK) Cells *innate lymphocytes involved in recognition of virally infected cells and tumour cells *have an invariant receptor *have cytotoxic granules that are released upon activation and induce apoptosis in the target cell *also major producers of interferons in the early stages of viral infections   Dendritic Cells *involved in uptake of the pathogen in the periphery and migration to the draining lymph node to present the antigen *only cell that can activate a naive T-cell *initiates the adaptive immune system